김지은 (The Hospital for Sick Children, University of Toronto)

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The Hospital for Sick Children, University of Toronto

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Immunity, Published:December 05, 2022 | https://doi.org/10.1016/j.immuni.2022.11.003 Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal development

Ji-Eun Kim,^1,2 Bo Li,³ Lijiang Fei,⁴ Rachael Horne,^5,6 Dorothy Lee,³ Adrian Kwan Loe,^1,2 Hiromu Miyake,³ Eda Ayar,^1,2 Dae-Kyum Kim,⁷ Michael G. Surette,⁸ Dana J. Philpott,⁹ Philip Sherman,^5,6 Guoji Guo,⁴ Agostino Pierro,³ and Tae-Hee Kim^1,2,10,*

¹Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
²Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
³General and Thoracic Surgery, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada
⁴Center for Stem Cell and Regenerative Medicine, Zhejiang University of School of Medicine, Hangzhou 310058, China
⁵Program in Cell Biology, Division of Gastroenterology, Hepatology & Nutrition, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
⁶Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON M5S 1A8, Canada
⁷Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
⁸Department of Biochemistry and Biomedical Sciences, Department of Medicine, McMaster University, 1280 Main St. W, Hamilton, ON L8S
4L8, Canada
⁹Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada
¹⁰Lead contact
^*Correspondence: Tae-Hee Kim

Abstract

Intestinal stem cell maturation and development coincide with gut microbiota exposure after birth. Here, we investigated how early life microbial exposure, and disruption of this process, impacts the intestinal stem cell niche and development. Single-cell transcriptional analysis revealed impaired stem cell differentiation into Paneth cells and macrophage specification upon antibiotic treatment in early life. Mouse genetic and organoid co-culture experiments demonstrated that a CD206+ subset of intestinal macrophages secreted Wnt ligands, which maintained the mesenchymal niche cells important for Paneth cell differentiation. Antibiotics and reduced numbers of Paneth cells are associated with the deadly infant disease, necrotizing enterocolitis(NEC). We showed that colonization with Lactobacillus or transfer of CD206+ macrophages promoted Paneth cell differentiation and reduced NEC severity. Together, our work defines the gut microbiota-mediated regulation of stem cell niches during early postnatal development.

논문정보

형식Research article
게재일2022년 12월 (BRIC 등록일 2022-12-07)
연구진국외 연구진
분야 생명과학 > 분자생물학

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